PSILOCYBIN therapy was found to be safe and well-tolerated in people with Parkinson’s disease and mood dysfunction, with clinically significant and sustained improvements in mood, cognition, and motor symptoms observed over several months.
Mood dysfunction is a common and challenging problem in Parkinson’s disease (PD), often preceding motor symptoms and predicting faster functional decline. Current treatments for depression and anxiety in PD are frequently ineffective, highlighting the urgent need for novel interventions. Psilocybin, a psychedelic compound, has shown promise in treating mood disorders but has not previously been tested in neurodegenerative diseases due to safety concerns. This open-label pilot trial aimed to evaluate the feasibility and safety of psilocybin therapy in individuals with mild to moderate PD who also experience depression and/or anxiety.
Twelve participants (average age 63.2 years, 5 women) received two doses of psilocybin (10 mg and 25 mg) combined with psychotherapy. No serious adverse events occurred, and no medical interventions were needed to manage the effects of psilocybin. The most common side effects were anxiety, nausea, and increased blood pressure, but these were mild and transient. Importantly, there was no worsening of Parkinson’s symptoms as measured by the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Instead, significant improvements were seen in non-motor symptoms (MDS-UPDRS Part I: –13.8 ± 1.3, p < 0.001), motor symptoms (Part II: –7.5 ± 0.9, p < 0.001; Part III: –4.6 ± 1.3, p = 0.001), and cognitive performance (notably in paired associates learning, spatial working memory, and probabilistic reversal learning). Baseline depression and anxiety scores (MADRS: 21.0 ± 8.7; HAM-A: 17.0 ± 3.7) improved to a clinically meaningful degree post-treatment, with benefits persisting at three months (MADRS: -9.3 ± 2.7, p = .001; HAM-A: –3.8 ± 1.7, p = 0.031).
In conclusion, this pilot study provides the first evidence that psilocybin therapy is feasible and potentially beneficial for mood and motor dysfunction in Parkinson’s disease, with sustained improvements and a favourable safety profile. For clinical practice, these findings suggest that psilocybin could become a valuable adjunct for managing mood and cognitive symptoms in PD, pending further research. Larger, controlled trials are now underway to explore the underlying mechanisms and confirm these promising results, with the aim of expanding treatment options for this underserved patient group.
Reference
Bradley ER et al. Psilocybin therapy for mood dysfunction in Parkinson’s disease: an open-label pilot trial. Neuropsychopharmacol. 2025;DOI:10.1038/s41386-025-02097-0.
